Studies on gastric mucosal cell injury induced by Helicobacter pylori.
The cause of gastric cell injury induced by Helicobacter pylori was investigated in vitro using gastric mucosal cells derived from male Japanese white rabbits. To evaluate the contribution of the potent urease activity of H. pylori to gastric mucosal cell injury, the supernatant of the H. pylori bacterial pellet, solubilized with N-octyl-glucoside, was added to the gastric mucosal cell suspension. Cell injury was assessed by lactate dehydrogenase (LDH) release into the extracellular fluid. Treatment of cells with H. pylori extracts together with urea resulted in high levels of LDH release, suggesting definite gastric mucosal cell injury, and elevation of ammonia concentration was also observed. In contrast, incubation with H. pylori extracts alone or urea solution alone did not result in increased LDH release or elevated ammonia concentrations. The degree of LDH release from gastric mucosal cells due to H. pylori extracts in the presence of urea was similar to that induced by administration of the same amount of exogenous ammonia. The addition of acetohydroxamic acid, a potent specific urease inhibitor, remarkably inhibited ammonia production, the elevation of pH of extracellular fluid, and LDH release in a dose-dependent manner. These results suggest that ammonia produced by potent urease activity of H. pylori in the presence of urea plays an important role in the pathogenesis of gastric mucosal cell injury.
Mitani-Ehara
S
S
Third Department of Internal Medicine, School of Medicine, University of Hokkaido, Sapporo, Japan.
Asaka
M
M
Katagiri
M
M
Nishikawa
K
K
Kudo
M
M
Takeda
H
H
D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D016481:Helicobacter Infections / Q000473:pathology*; D016480:Helicobacter pylori / Q000201:enzymology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011817:Rabbits; D014510:Urease / Q000378:metabolism
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C006358:acetohydroxamic acid; D000641:Ammonia; D007770:L-Lactate Dehydrogenase; D014510:Urease